RNAPII response to transcription‐blocking DNA lesions in mammalian cells

Jianming Wang, Martina Muste Sadurni, Marco Saponaro

Research output: Contribution to journalArticlepeer-review

Abstract

RNA polymerase II moves along genes to decode genetic information stored in the mammalian genome into messenger RNA and different forms of non-coding RNA. However, the transcription process is frequently challenged by DNA lesions caused by exogenous and endogenous insults, among which helix-distorting DNA lesions and double-stranded DNA breaks are particularly harmful for cell survival. In response to such DNA damage, RNA polymerase II transcription is regulated both locally and globally by multi-layer mechanisms, whereas transcription-blocking lesions are repaired before transcription can recover. Failure in DNA damage repair will cause genome instability and cell death. Although recent studies have expanded our understanding of RNA polymerase II regulation confronting DNA lesions, it is still not always clear what the direct contribution of RNA polymerase II is in the DNA damage repair processes. In this review, we focus on how RNA polymerase II and transcription are both repressed by transcription stalling lesions such as DNA-adducts and double strand breaks, as well as how they are actively regulated to support the cellular response to DNA damage and favour the repair of lesions.
Original languageEnglish
JournalThe FEBS journal
Early online date22 Jun 2022
DOIs
Publication statusE-pub ahead of print - 22 Jun 2022

Bibliographical note

Funding Information:
This work was supported by the University of Birmingham a BBSRC Responsive Mode grant (BB/S016155/1) and Cancer Research UK (C17422/A25154).

Publisher Copyright:
© 2022 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Keywords

  • DNA damage
  • R-loop
  • RNA polymerase II
  • RNA transcription
  • double strand break
  • homologous recombination
  • nucleotide excision repair

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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